Mosunetuzumab with response-adapted polatuzumab vedotin + obinutuzumab in previously untreated FL or MZL

Results from a single-center, open-label, phase II trial (NCT05169658) investigating  mosunetuzumab with positron emission tomography (PET)-response-adapted polatuzumab vedotin + obinutuzumab in patients with previously untreated follicular lymphoma (FL; n = 37) or marginal zone lymphoma (MZL; n = 5) were published in the Journal of Clinical Oncology by Lynch et al. In Part A, patients received mosunetuzumab monotherapy; patients without a complete response (CR) after Cycle 8 proceeded to Part B, where they received polatuzumab vedotin + obinutuzumab. The primary endpoint was the CR rate at the end of all protocol-defined therapy, and the secondary endpoint was overall response rate (ORR).

Key data: The end-of-treatment best ORR was 100%, with a CR rate of 86%. Mosunetuzumab monotherapy achieved an ORR and a CR rate of 100% and 71%, respectively. At a median follow-up of 34 months, the 2-year progression-free survival (PFS) rate was 89% (95% confidence interval [CI], 80–100) and was similar between patients with Grade 1–2 FL (89%), Grade 3A FL (86%), and MZL (100%). The 2-year overall survival (OS) rate was 100%. Cytokine release syndrome (CRS) occurred in 64% of patients (all Grade 1), and infections occurred in 57% of patients. Serious adverse events (SAEs) were reported in five patients. 

Key learning: Mosunetuzumab, with PET-response-adapted polatuzumab vedotin + obinutuzumab for patients not achieving CR, demonstrated encouraging responses and PFS rates, with a manageable safety profile in patients with previously untreated FL or MZL, supporting evaluation in larger, randomized studies.